Screening Platform For Development Of Antibody-Drug Conjugates Against Novel Targets At The National Research Council Of Canada

One of the most promising of the next generation of biologic-based cancer therapeutics builds on the molecular targeting abilities of antibodies by combining them with drugs to generate highly specific antibody-drug conjugates (ADCs). However, the development of ADCs requires time-consuming selection of the antibody for every target and cancer type. High-throughput screening technologies based on the use of conjugated secondary antibodies provide a fast and efficient surrogate assay from which to identify which antibodies are best internalized and suitable for immunoconjugate development into ADCs. As part of its integrated antibody development initiative, NRC has isolated and characterized anti- mouse Fc and anti-human Fc monoclonal antibodies to serve as very selective detective reagents for various IgG isotypes. We have shown that these secondary antibodies are species specific, selective and of high affinity. When conjugated to pH sensitive fluorophores, we have used them to specifically identify internalizing antibodies against tumor targets, which were later validated as ADCs. Furthermore, these secondary conjugates exhibit high specific potency and low background toxicity once conjugated to linkered drugs. This approach allow us to optimize the selection of an antibody for a particular target, tumor type, linker and drug for ADC development. NRC will present results of a screen of 285 mouse antibodies against 20 different targets in 7 different cancer cell lines, using either MCC-DM1 or vc-MMAE-conjugated secondary antibodies. The NRC ADC discovery platform is combining this methodology with our proprietary mRNA and DNA expression database for the selection of appropriate ADC targets. NRC Biologics and Biomanufacturing program is in the process of screening thousands of NRC antibodies generated against a variety of cancer-associated cell surface targets to deliver a steady pipeline of ADCS as part of its drug discovery efforts. This functional screening platform further promotes the integration and advancement of NRC’s capabilities and strengths in the area of biologic-based therapeutics lead candidate selection, including quality attributes and characterization and biomanufacturing. The combined expertise in cell biology, high throughput screening, antibody generation and selection, bioinformatics and expression analysis forms the foundation by which NRC can establish strategic collaborations with other Canadian or international partners to develop antibodies into novel ADC biologics. Citation Format: Maria Luz Jaramillo, Luc Meury, Patrice Bouchard, Allan Matte, Anne Marcil, Mauro Acchione, Jennifer Hill, Francois Fauteux. Screening platform for development of antibody-drug conjugates against novel targets at the National Research Council of Canada [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3669. doi:10.1158/1538-7445.AM2017-3669